Hansen Malene, Rubinsztein David C, Walker David W
Sanford Burnham Prebys Medical Discovery Institute, Program of Development, Aging and Regeneration, La Jolla, CA, USA.
Cambridge Institute for Medical Research, Department of Medical Genetics, Cambridge, UK.
Nat Rev Mol Cell Biol. 2018 Sep;19(9):579-593. doi: 10.1038/s41580-018-0033-y.
Autophagy is a conserved process that catabolizes intracellular components to maintain energy homeostasis and to protect cells against stress. Autophagy has crucial roles during development and disease, and evidence accumulated over the past decade indicates that autophagy also has a direct role in modulating ageing. In particular, elegant studies using yeasts, worms, flies and mice have demonstrated a broad requirement for autophagy-related genes in the lifespan extension observed in a number of conserved longevity paradigms. Moreover, several new and interesting concepts relevant to autophagy and its role in modulating longevity have emerged. First, select tissues may require or benefit from autophagy activation in longevity paradigms, as tissue-specific overexpression of single autophagy genes is sufficient to extend lifespan. Second, selective types of autophagy may be crucial for longevity by specifically targeting dysfunctional cellular components and preventing their accumulation. And third, autophagy can influence organismal health and ageing even non-cell autonomously, and thus, autophagy stimulation in select tissues can have beneficial, systemic effects on lifespan. Understanding these mechanisms will be important for the development of approaches to improve human healthspan that are based on the modulation of autophagy.
自噬是一个保守的过程，它分解细胞内成分以维持能量稳态并保护细胞免受应激。自噬在发育和疾病过程中发挥着关键作用，过去十年积累的证据表明自噬在调节衰老方面也具有直接作用。特别是，使用酵母、蠕虫、果蝇和小鼠进行的出色研究表明，在许多保守的长寿模式中观察到的寿命延长对自噬相关基因有广泛需求。此外，出现了几个与自噬及其在调节寿命方面的作用相关的新的有趣概念。首先，在长寿模式中，特定组织可能需要自噬激活或从中受益，因为单个自噬基因的组织特异性过表达足以延长寿命。其次，选择性自噬类型可能通过特异性靶向功能失调的细胞成分并防止其积累对长寿至关重要。第三，自噬甚至可以非细胞自主地影响机体健康和衰老，因此，特定组织中的自噬刺激可以对寿命产生有益的全身影响。了解这些机制对于开发基于自噬调节的改善人类健康寿命的方法至关重要。
